Chad Brouwer

Bio: Chad Brouwer is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Hydroamination & Homogeneous catalysis. The author has an hindex of 11, co-authored 18 publications receiving 2309 citations. Previous affiliations of Chad Brouwer include University of Illinois at Chicago & University of Chicago.

Gold-catalyzed organic transformations.

Abstract: Thanks to its unusual stability, metallic gold has been used for thousands of years in jewelry, currency, chinaware, and so forth. However, gold had not become the chemists’ “precious metal” until very recently. In the past few years, reports on gold-catalyzed organic transformations have increased substantially. Thanks to gold-based catalysts, various organic transformations have been accessible under facile conditions with both high yields and chemoselectivity.

Efficient gold-catalyzed hydroamination of 1,3-dienes.

Abstract: Homogenous gold catalysis has proven to be a powerful tool in organic synthesis in recent years. 2] Gold(i) and gold(iii) are soft and hence carbophilic Lewis acids, which can activate unsaturated C C bonds toward nucleophilic attack. Despite much success in alkyne activation, the activation of olefins by gold ions has remained relatively unexplored. Our group recently showed that phenols and carboxylic acids can undergo intermolecular addition to inert olefins in the presence of Ph3PAuOTf (Tf= trifluoromethanesulfonyl). [3] This represents a rare example of carbon–heteroatom bond formation by the gold-catalyzed activation of inert olefins. This method can be extended to the hydroamination of simple alkenes (Scheme 1). These types of transformations have

Neuroinflammation in Temporal Lobe Epilepsy Measured Using Positron Emission Tomographic Imaging of Translocator Protein

Abstract: Importance Neuroinflammation may play a role in epilepsy. Translocator protein 18 kDa (TSPO), a biomarker of neuroinflammation, is overexpressed on activated microglia and reactive astrocytes. A preliminary positron emission tomographic (PET) imaging study using carbon 11 ([ 11 C])–labeled PBR28 in patients with temporal lobe epilepsy (TLE) found increased TSPO ipsilateral to seizure foci. Full quantitation of TSPO in vivo is needed to detect widespread inflammation in the epileptic brain. Objectives To determine whether patients with TLE have widespread TSPO overexpression using [ 11 C]PBR28 PET imaging, and to replicate relative ipsilateral TSPO increases in patients with TLE using [ 11 C]PBR28 and another TSPO radioligand, [ 11 C]DPA-713. Design, Setting, and Participants In a cohort study from March 2009 through September 2013 at the Clinical Epilepsy Section of the National Institute of Neurological Disorders and Stroke, participants underwent brain PET and a subset had concurrent arterial sampling. Twenty-three patients with TLE and 11 age-matched controls were scanned with [ 11 C]PBR28, and 8 patients and 7 controls were scanned with [ 11 C]DPA-713. Patients with TLE had unilateral temporal seizure foci based on ictal electroencephalography and structural magnetic resonance imaging. Participants with homozygous low-affinity TSPO binding were excluded. Main Outcomes and Measures The [ 11 C]PBR28 distribution volume ( V T ) corrected for free fraction ( f P ) was measured in patients with TLE and controls using FreeSurfer software and T1-weighted magnetic resonance imaging for anatomical localization of bilateral temporal and extratemporal regions. Side-to-side asymmetry in patients with TLE was calculated as the ratio of ipsilateral to contralateral [ 11 C]PBR28 and [ 11 C]DPA-713 standardized uptake values from temporal regions. Results The [ 11 C]PBR28 V T to f p ratio was higher in patients with TLE than in controls for all ipsilateral temporal regions (27%-42%; P P 11 C]PBR28 uptake exceeding the 95% confidence interval of the controls. Binding of [ 11 C]PBR28 was increased significantly in thalamus. Relative [ 11 C]PBR28 and [ 11 C]DPA-713 uptakes were higher ipsilateral than contralateral to seizure foci in patients with TLE ([ 11 C]PBR28: 2%-6%; [ 11 C]DPA-713: 4%-9%). Asymmetry of [ 11 C]DPA-713 was greater than that of [ 11 C]PBR28 ( F = 29.4; P = .001). Conclusions and Relevance Binding of TSPO is increased both ipsilateral and contralateral to seizure foci in patients with TLE, suggesting ongoing inflammation. Anti-inflammatory therapy may play a role in treating drug-resistant epilepsy.

Gold-Catalyzed Organic Reactions

Abstract: Although homogeneous gold catalysis was known previously, an exponential growth was only induced 12 years ago. The key findings which induce that rise of the field are discussed. This includes early reactions of allenes and furanynes and intermediates of these conversions as well as hydroarylation reactions. Other substrate types addressed are alkynyl epoxides and N-propargyl carboxamides. Important vinylgold intermediates, the transmetalation from gold to other transition metals, the development of new ligands for gold catalysis, and significant contributions from computational chemistry are other crucial points for the field highlighted here.

Catalytic Carbophilic Activation: Catalysis by Platinum and Gold π Acids

Abstract: The ability of platinum and gold catalysts to effect powerful atom-economic transformations has led to a marked increase in their utilization. The quite remarkable correlation of their catalytic behavior with the available structural data, coordination chemistry, and organometallic reactivity patterns, including relativistic effects, allows the underlying principles of catalytic carbophilic activation by π acids to be formulated. The spectrum of reactivity extends beyond their utility as catalytic and benign alternatives to conventional stoichiometric π acids. The resulting reactivity profile allows this entire field of catalysis to be rationalized, and brings together the apparently disparate electrophilic metal carbene and nonclassical carbocation explanations. The advances in coupling, cycloisomerization, and structural reorganization—from the design of new transformations to the improvement to known reactions—are highlighted in this Review. The application of platinum- and gold-catalyzed transformations in natural product synthesis is also discussed.